VetInfo Digest -  May 2002

This Month:

"In-house" Test Procedures

Fecal Examination

Heartworm Tests

Feline Leukemia

Feline Immunodeficiency Virus

Ehrlichiosis

Lyme Disease

Why Use Medications That Might Cause Harm?

 

This Month's Note:

There are a number of laboratory tests that are available to veterinarians for use in the office, rather than being sent to outside laboratories. Fecal examinations, heartworm tests, feline leukemia tests, feline immunodeficiency virus tests and many other "in house" test procedures are available to improve the care of pets. Veterinary clients sometimes question the need for testing and sometimes ask for tests that don't seem appropriate for their pets. Explanations of the usefulness of a test, its limitations and the reasons for performing a particular test are often not clear to veterinary clients. So this month we are going to cover the most common testing procedures utilizing the in-house test kits.

Most of the tests involving blood are ELISA tests, which is an acronym for enzyme-linked immunosorbent assay tests. These are quick screening tests that can be used to detect antigens, such as viruses or heartworms or for antibodies against antigens such as viruses and bacteria. The major difference between an antigen test and an antibody test is that the presence of an antigen, barring false positive results, generally confirms an infection. The presence of antibodies only indicates exposure to the antigen the antibody is linked to. Therefore, antibody tests can be less meaningful in some cases but work well in other instances.

Fecal Examination

Stool samples may contain worm eggs, which are identifiable by their structure. A roundworm egg looks different than a hookworm egg and both are different from whipworm eggs. It is rare to see actual worms in a stool sample but this occasionally occurs. Tapeworm egg sacs, which are about 1cm in length and often move, can be seen in the stool when they are present. Feces may also contain various stages of the life cycle of protozoan parasites, which may be cysts or small motile organisms. Bacteria are a normal inhabitant in stool samples. It is tempting to try to evaluate the overall number of bacteria or the bacterial types by direct examination but this is supposed to be unreliable. It is possible to identify certain bacterial types in the stool through the use of staining procedures, though. Fleas are sometimes identified in stool samples when they can not be found on the pet's body, especially in the case of pets with flea allergy who become very adept at removing the fleas by licking and chewing.

There are several ways to examine the stools and each has advantages and disadvantages.

A direct fecal examination is made by mixing a small amount of stool, often off of a rectal thermometer, with a small amount of saline. This is a very inefficient way to look for worms because worm eggs are not widely distributed in most stool samples. Saline smears are a very good way to look for giardia infestation and other protozoan infections, though. The motile stages of these parasite's life cycles are often highly visible using this technique. When pets have diarrhea it makes sense to examine a saline smear as part of the stool examination process.

Fecal floatation is the most commonly performed stool examination in most veterinary practices. This technique takes advantage of the tendency of worm eggs, coccidia cysts and giardia cysts to float in certain solutions. There are several ways to perform the procedure, some of which favor finding worm eggs and some of which favor finding the giardia organisms. This test requires a more substantial stool sample because the feces is mixed with the floatation solution and then centrifuged or allowed to stand for several moments to make the eggs and cysts float to the surface of the solution. A microscope cover slip is then used to collect the top layer of the solution for examination. The larger sample size and concentration of the worm eggs floating in the solution makes it more likely that worms will be identified in a fecal floatation sample than with the direct examination in saline. If you are asked to collect a sample for fecal floatation it is best if the sample is less than 4 hours old and it takes about a teaspoonful of stool for the examination.

Despite the ability to find eggs and cysts better in floatation samples, this technique is still limited by the need for the eggs or cysts to be present in that particular stool sample in order to be identified. Coccidia and giardia are shed intermittently and worm egg burdens vary widely in the stool. It is not unreasonable for your veterinarian to repeat fecal floatation several times in the course of trying to diagnose chronic diarrhea, chronic weight loss or other conditions that might be due to intestinal parasites.

Tapeworms are not easily identified with fecal samples. If your veterinarian fails to identify a tapeworm infestation through fecal examination it is not because the test is not being done properly. Fecal examination is just a poor test for this particular type of worm.

It is also possible to identify certain types of bacterial infection by examination of a small amount of feces smeared on a microscope slide and stained with appropriate stains. Most veterinary practices have quick blood stains that can be used to aid in the diagnosis of clostridial infections. Some veterinary hospitals also use acid-fast stains to help identify Campylobacter infections which cause chronic diarrhea in some pets.

When chronic gastrointestinal disease is present or when acute disease seems severe, all three forms of fecal examination are warranted in the effort to rule out as many causes as possible.

 

Heartworm Testing

Heartworms can be detected in many dogs by examination of a drop of blood for baby heartworms, or microfilaria. If this were the only available test procedure many cases of heartworm disease in dogs and almost all cases of heartworms in cats would be missed, though. Microfilaria are only present when there are adult heartworms of both sexes present in the pet's body in order for baby heartworms to be produced. Microfilaria are uncommon in heartworm infections in cats and dogs are often capable of suppressing heartworm reproduction or of killing the microfilaria. There is another species of worm that produces microfilaria (Dipetelonema reconditum) that can be found in the blood stream so it is important to confirm that the microfilaria seen in the blood are actually heartworms.

The first attempt to improve the success of heartworm testing was the development of concentration tests so that a larger blood sample could be examined for microfilaria. The most common concentration test used in practice presently are filtration tests in which the red blood cells are lysed so that they can be flushed through a microfilter. If microfilaria are present they are retained on the filter surface which is examined microscopically for their presence. The original concentrating test for microfilaria was the Knott's test, which involves centrifuging the blood and examining for microfilaria. Some type of examination for microfilaria is best prior to administering a daily heartworm prevention medication such as Filaribits Plus (tm), since serious reactions can occur if microfilaria are present.

Many dogs with heartworms, perhaps as many as 40%, do not have microfilaria. Very few cats have microfilaria. This led to the development of antibody tests for heartworm exposure. The antibody tests are still commonly used in cats. It is important to recognize that these tests only show exposure to heartworm antigen. They do not indicate a current infection. This is especially important in cats because many cats have partial development of heartworms and then the heartworms die, resulting in antibody production but no active heartworm infection. It is possible to test directly for heartworm antigen. In dogs this has become the standard test. However, these tests tend to require the presence of more than one or two worms to be positive and cats often have two or fewer heartworms causing their clinical signs. So for cats, antibody testing as a screening test is still justifiable, but infection should be confirmed with antigen testing, ultrasound examination, X-rays or some other supporting evidence.

Antigen tests are the current standard for heartworm testing in dogs. These tests can detect cells from the uterine lining of adult female heartworms. Since it takes approximately 6 to 7 months for female heartworms to mature to the point that they shed these cells, there is no justification for testing for heartworms using an antigen test prior to the time a puppy is 6 months old. An obvious limitation of this test is that it can not detect heartworm infections in which there are only male heartworms. Fortunately, this does not appear to be a major problem. Unless there are obvious clinical signs of heartworm disease it is best to try to confirm the presence of a heartworm infection when a positive test result is obtained. This is especially true in regions in which heartworm infection is possible, but not highly likely. Infection can be confirmed if there are significant changes on X-rays of the chest, ultrasound examination reveals worms or if a different testing method shows heartworm disease, as well.

It is not necessary to do a heartworm test in cats prior to starting preventative medications. Many of our clients ask us why not, since we do insist on testing adult dogs prior to starting preventative medications. The heartworm prevention medications sometimes cause reactions when microfilaria are present, which is much more likely in dogs than it is in cats. In addition, there is a treatment for heartworms in dogs and it is important to treat as early as possible in the infection. We do not have a safe and effective heartworm treatment for cats at this time. It is sometimes important to know if heartworms are causing clinical signs in a cat. The best screening test for heartworms in cats are the antibody tests. While these tests are not conclusive, they do indicate whether exposure to heartworms has occurred. If the antibody test is positive and there are clinical signs of heartworm disease then further testing should be considered. Ultrasound examination, X-rays and antigen testing can all contribute to the diagnosis of heartworm disease in cats. It may be necessary to use more than one of these tests to confirm an infection since cats may have clinical signs associated with one worm and it is difficult to detect a single worm with any individual test.

The necessity for routine heartworm examination is another thing that clients sometimes question us about. Is it really necessary to test for heartworms periodically in a dog receiving the heartworm preventative medications on a regular basis? There are good reasons to do routine testing for heartworms. Some dogs do not swallow the heartworm medication even though it is given to them. Some dog owners forget to give the medication occasionally. But even if these things did not occur there is a good chance that heartworms will some day become resistant to one or more of the preventative medications. If this resistance is not discovered early, many dogs will be harmed by development of heartworm disease unnecessarily. It may not seem entirely fair, but veterinarians and the pharmaceutical companies are asking pet owners to participate in a large survey of the effectiveness of heartworm preventatives by having their dogs examined on a regular basis. It is the only way to pick up on a break in effectiveness early enough to protect the majority of dogs at risk for heartworm disease. At the present time the American Heartworm Society ( http://www.heartwormsociety.org/ ) recommends testing all dogs on heartworm prevention medications every two to three years for dogs who have been on proper dosages of heartworm prevention during the appropriate time of the year in their geographic region and are on the monthly or injectable heartworm prevention medications. Most state veterinary boards are content that proper medical procedure has been followed if the AHS guidelines are followed and the patient is seen by the veterinary practice at least annually, when monthly preventative medications are used. This should also meet the guidelines for proper dispensing of a prescription medication, which is the other reason that many veterinary practices insist on routine heartworm examinations even when it seems likely that the patient has received the medication on the proper schedule. For dogs on daily preventative medications such as Filaribits Plus (tm) it is best to test yearly, especially if the medication is only given part of the year. If these medications are given to a dog with microfilaria serious reactions, including death, can occur.

I think that it is either unethical, or an indication of poor understanding of heartworm disease, for a veterinary practice to test a puppy for heartworms prior to six months of age. In either case, it seems to me that a routine policy of testing younger puppies for heartworms prior to dispensing heartworm prevention medications is sufficient reason to consider changing veterinarians.

 

Feline Leukemia Virus Testing

Testing for feline leukemia virus is done in-house by most veterinary clinics and is often done as a screening test to rule out FeLV infection in kittens or newly acquired adult cats. When a feline leukemia test is negative, the result is considered to be very accurate, although there is a small possibility of a hidden or latent infection. When a feline leukemia test is positive, especially during routine screening, it is necessary to retest using a different test method prior to accepting the result. It is estimated that a positive feline leukemia test in a cat without clinical signs is inaccurate as much as 50% of the time -- or more. In cats with clinical signs suggestive of FeLV the false positive rate is much lower, probably less than 10%.

Feline leukemia virus testing is not age dependent, since the virus is tested for directly. This means that it is acceptable to test kittens at any age.

FeLV is a frustrating condition for veterinarians because it is difficult to completely rule out, due to the ability of this virus to hide in the bone marrow and be "invisible" to testing. For this reason, it is considered to be good medical practice to test for feline leukemia virus infection whenever a cat exhibits clinical signs suggestive of the disease, even if they have been tested more than once previously. This can get frustrating for cat owners and for veterinarians alike. In our practice, we had a cat who tested faintly positive for feline leukemia when he was about four months old. Each time he was ill we tested him again, due to the previous positive result. Three tests in a row he tested negative for FeLV over the years. Finally, when he was eleven years old, he became very ill and tested strongly positive for feline leukemia virus. Due to the previous negative tests we confirmed the diagnosis with IFA (more specific) testing, anyway. He was truly positive at this time. Cases like this make it hard not to test for FeLV when a cat is ill --- even when there have been negative tests previously.

Whether or not to test a cat when FeLV infection is not highly likely but signs are present is a judgment call that you and your vet will have to make. However, it is not unreasonable for your veterinarian to ask about testing, or retesting, for this virus in a cat that is obviously ill without an apparent cause.

The other major difficulty with testing for FeLV is the use of ELISA tests in healthy kittens and cats as a screening test for the presence of this infection. FeLV can be an nonapparent infection. It makes sense to try to protect other kittens or cats in the household from the possibility of introducing FeLV. It is also reasonable to test a newly acquired kitten in order to prevent later heartache if the kitten does test positive. Many kittens with no obvious signs of FeLV are tested for the virus for these and similar reasons.

When using a test as a screening test it is important to understand that a positive test result is not nearly as meaningful as it is in a symptomatic cat. It is estimated that as many as 1/2 of the positive test results from cats who appear healthy are false positive results. For an explanation of why this occurs please check out the November 2000 issue of the VetInfo Digest in the subscriber area at this address: (http://www.vetinfo.com/subscriber/1100digest.html). It is very easy to forget the big picture when faced with visual evidence of a positive test result. Do not condemn a healthy kitten to death because of a single positive ELISA feline leukemia test result. Confirm this result with alternative test procedures before making any decision about its meaning.

 

Feline Immunodeficiency Virus

Testing for feline immunodeficiency virus utilizes an antibody test, not an antigen test. This is not as important a difference in the case of FIV as it is for some other viral illnesses, because the disease is lifelong and exposure sufficient to cause antibody production almost always indicates a true infection. However, there is a significant false positive rate with this test due to overlap in the antibodies for this and other diseases and it is always best to confirm a positive test obtained with an ELISA in-house test using Western Blot testing. The Western Blot test, run by specialized laboratories, tests for several antibodies associated with FIV and is therefore more accurate. This is particularly true when euthanasia is a consideration or when a cat lives in a multi-cat household or poses a risk to other cats in some other way.

Testing kittens for FIV is more complicated. Kittens absorb antibodies to various diseases, possibly including FIV if the mother has the disease, from the colostrum (first milk). These antibodies persist for some time in the body, up to four months in the case of FIV. Since the test detects antibodies rather than the virus, this presents major problems in determining the FIV status of a kitten. The American Association of Feline Practitioners still recommends testing kittens for this virus before bringing them into the household, with the understanding that the test may not represent an actual infection. However, their thought process is that it does indicate the potential for infection and the need to prevent transmission to other cats. FIV is primarily spread through bite wounds, so preventing physical contact would prevent spread of the disease. To determine whether or not a positive test in a kitten is a true infection it is necessary to wait until the kitten is at least 4 months of age and some vets feel more comfortable waiting until 5 or 6 months of age.

It is best to confirm all positive tests for FIV that are done using test kits available to general veterinary practitioners through Western blot testing, but this is especially important when there is the potential for exposure of other cats by the infected cat.

 

Ehrlichiosis

There is a relatively new test for in-clinic use that includes heartworm testing, ehrlichiosis testing and Lyme disease testing. I believe that this test was introduced in 1999 or 2000 and is now being used around the country on a variable basis.

This is a test for antibodies to the Ehrlichia canis organism. The test appears to be pretty accurate (low false positive rate). However, like all antibody tests it indicates exposure to the organism rather than the presence of the organism in the body. This makes interpretation of the test pretty difficult. This is especially true for ehrlichiosis because it can cause chronic low level infections in dogs despite apparently successful therapy and because a large number of dogs who test positive for antibodies never have recognized disease symptoms. Whether they have disease symptoms that go unrecognized is hard to say. This also makes it hard to decide whether there is any validity to treatment based solely on elevated titers. At the present time there is no clear consensus among the experts in infectious disease on these issues. So the value of the test for an individual patient is uncertain at the present time, although being aware of exposure is at least of some benefit.

On the other hand, testing a large group of dogs in a practice to establish whether ehrlichiosis is a problem in the area and to get a firm idea of the number of dogs with antibodies against the disease is very helpful in evaluating clinical cases in which symptoms do show up. So this may work out to be a test much like the heartworm test, in which the test may be more valuable in promoting the general health of all dogs than of the specific dog being tested.

When a dog has clinical symptoms of ehrlichiosis it makes sense to test for the disease. A quick in house test to determine if ehrlichosis is at least likely seems worthwhile. More specific testing by a lab that offers PCR or serology testing would still be a good idea for positive cases and even some of the negative ones when the clinical signs really seem to be a match for ehrlichiosis.

 

Lyme Disease

Lyme disease testing is very much like ehrlichiosis testing. The in-house test from Idexx is an antibody test. It avoids a previous problem of false positives due to previous vaccination by testing for an antibody that does not occur after vaccination but still only indicates exposure to the disease, not a current infection. It too seems good for quick analysis of suspected cases and for gaining a general idea of the prevalence of Lyme disease in an area. Again, a positive titer may not indicate a need to actually treat the patient, though. It may be an indication of exposure to the bacteria without actual infection. Over time it may become more clear exactly what a positive screening test means for any particular individual. It would be best to confirm all positive tests at the present time using a different testing method, such as Western blot testing, and to think about the necessity of treatment based on the overall health and clinical signs of the patient. It is unlikely that all dogs with positive Lyme disease titers require treatment.

 

General Principles

No matter what tests are run it is critically important to recognize several things about laboratory testing and particularly about screening tests. Veterinarians and pet owners both prefer to treat disorders based on results of lab tests. Something about having a test result infers a certainty of diagnosis that is reassuring. It would be really nice if that certainty held up under scrutiny but for many tests it simply doesn't. This can be due to false positives on testing, lab error (even with the simple in-house test kits there is room for error), the presence of more than one disease and the uncertainty of the meaning of test for antibodies instead of antigens. When you or your vet is suspicious of a test result the best course of action is usually to retest using a different testing method, if possible. This is especially true for screening tests that are used to check for nonapparent diseases in otherwise healthy pets. Understanding the limitations of the in-house tests is difficult and it is hard for veterinarians to run a test, get positive results and then try to explain why those results might not be certain. It makes may pet owners want to ask, "Why run the test, then?" The best answer I can give is that it is better to have as much information as possible when making a clinical assessment. It is just really important to understand the limitations of that information and to be careful to act accordingly.

 

Why Use Medications That Might Cause Harm?

Clients often ask me if a medication that I propose to use to treat their pet might cause harm. The answer is almost always yes. There are side effects that can occur with most medications. Serious side effects that cause debilitation or death are usually rare. For most medications the side effects are more of an inconvenience than a threat to the pet. However, for some medications side effects are very common and for a select few the potential for death with use can be as high as 2 or 3%.

Why would a veterinarian use a medication that might cause death? In most cases the reason is because there isn't a lot of choice if a condition is to be treated. In some instances the reasoning has more to do with economics. As an example, if I have lab results from an infection on a dog's foot that suggest that sulfa-trimethoprim antibiotics or fluoroquinolones are likely to work, which should I pick? The sulfa drugs can have serious side effects, including life threatening immune mediated thrombocytopenia. However, these effects are rare with proper dosing and short term use. The sulfa drugs cost about $14 for our patient. Fluoroquinolones are generally recognized as a safer alternative in dogs but do have some side effects. The cost for our patient for the same time period is likely to be $80. Either drug is likely to work. So is a small risk of a serious problem more important than the cost difference? For many of my clients it would be, but most of my clients would choose the less expensive medication, accepting a small risk of problems as acceptable rather than spending more on medications.

Cost is only one factor in this sort of decision making, though. There are very few medications that are effective for treating an illness or disorder and for which no side effects are known. It may be necessary to make a choice between a medication that causes death in rare instances and a medication that commonly causes serious but nonfatal side effects. Making many pets sick to avoid the risk of killing one in ten thousand pets is a hard choice to make. It is bad for the pet that dies but is it really necessary to make a hundred cats suffer serious side effects to avoid that possibility?

Veterinarians have a different perspective on medications than veterinary clients. We see the good that medications do on a daily basis and we see reactions to them much less frequently. Our experiences tend to lull us into a false sense of security, giving the feeling that serious side effects are something that happens to the patients of other veterinarians. Only rarely does a serious reaction occur that causes us to rethink this situation.

Veterinary clients only see the results of medications for their own pets, or perhaps a few other pets owned by neighbors and friends. When a reaction does occur, the client doesn't have the perspective of seeing hundreds of pets improve on a medication. They just know that it harmed their pet. Given this perspective, it is easy to see why some veterinary clients become extremely upset over reactions to medications. Sometimes they sue the veterinarian or the drug manufacturer. Sometimes they write letters to publications or set up web sites on the Internet denouncing a drug or drug company. When you see this type of information it is easy to get nervous about using a medication, or sometimes any medication, to treat a pet's illness.

As a veterinarians, I can't stop using medications that might cause reactions because it would simply mean that I have to stop practicing effective medicine. So I become used to the possibility of a problem and live with it, much like commuters do with their drive to work. Every commuter knows that getting in the car and going to work is dangerous. But they have to work. So they do it. On a day to day basis they don't think a lot about the risk they are taking. When they are in an accident, though, the risk becomes more real. But most of them get back in their cars again and drive to work as soon as they can, because they have to in order to provide for themselves and their families.

I know that medications can sometimes cause harm. But I have to have medications in order to have an effective practice, so I use them day in an day out. I don't want to harm any pets but I realize that if I want to help any of them, I have to take on some risk of harming a few individual pets.

As hard as it is to do, it is necessary to look at the benefits of medications for the whole population affected by a condition the medications treat. Heartworm treatment medications and the effects they cause through killing heartworms cause approximately 1 to 3% of pets treated with the medications to die. On the other hand, heartworm infection probably kills about 80% of the dogs that are infected. So even though the medications aren't perfect, they are a lot better than the alternative of not treating over fear of death due to the treatment.

Another factor in the use of medications that people have difficulty with is coincidence. If a pet is treated in any way, things that happen to it over the next few days are often blamed on the medication. People are used to looking for a cause when something affects them. A client called me at home this week and asked if the vaccine I injected her cat with that afternoon could have poisoned it and caused it to develop cystitis, since it was visiting the litter pan frequently after the visit to our office. Heartworm prevention medications get blamed for many similar problems, simply because they are given once a month. Anything that happens to the pet within a week may cause the pet owner to ask me if it was due to the heartworm prevention medications. The best answer I can give is that any 30 to 84 days of the year that are arbitrarily chosen will be the days that some pets get ill and other pets die. It would be pretty easy to prove that Thursdays were fatal to pets if the only coincidence we were seeing was the fact that roughly 14 per cent of pets die on Thursdays. Sometimes the problems that are seen as side effects of a medication are simply the result of coincidence.

I have corresponded with people who are serious about banning the use of some medications that are extremely valuable. Carprofen (Rimadyl Rx) helps many older dogs live in comfort. It does cause serious liver disease in a very small number of dogs, though. Some of these dogs have died. I can relate to this issue personally. I take Vioxx (Rx) for chronic back pain from an old injury. I know that there are some serious risks associated with the use of Vioxx, including death, but I take them willingly. Relief from chronic pain is really worth the risk, to me. If I make the same ethical judgment for the pets that I treat, I believe that I am making the decision with due care, as long as I have discussed the risk with my clients and they concur in the decision. I have seen dozens of dogs and cats die from heartworm disease. Even if heartworm prevention medications do cause some pets to die, which hasn't been proven to be the case, it would be an easy decision for me to use them. Many more pets live comfortable long lives due to the availability of heartworm medications than are harmed by them.

There is a very long list of medications that have great benefits at the cost of some serious side effects. Every day veterinarians have to balance the risk of these side effects against the value of the medication to the patient. In some instances, we make a choice that causes an individual pet harm. We can live with this only because we see the benefits in so many other pets. I know that individual pet owners don't have the opportunity to see the number of cases that I do. It is easy to see why they are so confused and angry over the reaction that their pet had. I just can't agree with their assessment that a medication that can cause harm should never be used. Veterinarians would have to give up practice if we stopped using any medications that might harm a patient. There simply wouldn't be enough effective medications to make practice possible. So we take some risk and get in our cars and we drive to work...... and then we make the same kind of decision all day while working with our patients.

 

Thanks for Your Support!

The VetInfo Digest is published by TierCom, Inc., P.O. Box 476, Cobbs Creek, VA 23035. The opinions expressed in this newsletter are those of Michael Richards, DVM., author. Please send e-mail for Dr. Richards to mervet@inna.net

Copyright 2002, TierCom, Inc.